Effect of colchicine, methotrexate, and hydroxychloroquine therapy on cardiovascular outcomes in patients with calcium pyrophosphate crystal deposition disease

Abstract

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake >20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure >III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index >25 kg/m2 and >30 kg/m2; cholesterol level (CHOL) >5.1 mmol/l; glomerular filtration rate (GFR) < 60 ml/min/1.73 m2; serum uric acid level >360 μmol/l; hypercalcemia (serum calcium level >2.62 mmol/L); CRP level >2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level >65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR <60 ml/min/1.73 m2 (OR 2.78; 95% CI 1.32–5.56), history of CVD (OR 2,32; 95% CI 1.22–4.44). COL therapy reduced the risk of cardiovascular events (OR 0.20; 95% CI 0.11–0.39).Conclusion. Poor CVD outcomes in CPPD are associated with age, hypercholesterolemia, chronic kidney disease, and a history of CVD. The use of COL, in contrast to MT and HC, was accompanied by a decrease in cardiovascular risk.